Network toxicological insights into PET exposure and bladder cancer development

To systematically evaluate the molecular associations between exposure to polyethylene terephthalate (PET) microplastics and the occurrence, progression, and prognosis of bladder cancer (BLCA) based on network toxicology and computational biology approaches. Potential targets of PET were predicted using SwissTargetPrediction and intersected with BLCA‑related genes to yield common targets for GO and KEGG enrichment analyses. Subsequently, a risk score model was constructed by screening key genes from the TCGA‑BLCA cohort via Cox regression and LASSO, with its predictive performance validated using external GEO datasets. Immune infiltration characteristics were simultaneously assessed using CIBERSORT. In addition, molecular docking and molecular dynamics simulations were performed to verify the binding stability between the target proteins and PET. A total of 86 common PET‑BLCA targets were identified, which were significantly enriched in tumor‑related signaling pathways such as cAMP and ErbB, as well as oxidative stress processes. The risk model incorporating six key genes (NQO1, AKR1B1, ADK, GAK, PDE5A, and MAPK10) successfully stratified patients into high‑ and low‑risk groups, with a significant survival difference ( P < 0.001). The expression of these genes may also be correlated with immune features including CD8⁺ T cells and macrophage polarization. Molecular docking revealed binding energies below − 5 kcal/mol for all targets, and molecular dynamics simulations further confirmed the conformational stability and sustained hydrogen‑bonding interactions of the complexes. PET may participate in BLCA progression by modulating multiple tumor‑related signaling pathways and reshaping the immune microenvironment. The prognostic model and the six key genes provide a verifiable candidate framework for mechanistic studies and risk assessment; however, further experimental validation is needed to establish causal relationships.